They simulated the reaction of a difluorocarbene molecule, which acts at the source of fluorine atoms, with various pairs of small molecules featuring a double or triple bond. The ability to attach fluorine atoms to the previously difficult-to-access 'alpha carbon'-the carbon immediately next to the nitrogen in the ring structure-could lead to the development of a host of novel drugs.īefore carrying out experiments in the lab, the researchers cast a wide net, computationally testing the viability of numerous 3-component reactions using the artificial force induced reaction (AFIR) method.

Researchers at ICReDD have utilized quantum chemical calculations to discover a reaction that selectively adds two fluorine atoms to a difficult-to-access position on an N-heterocycle- molecules with a carbon ring structure where at least one carbon in the ring is replaced with nitrogen.

The presence and position of fluorine in a molecule often affects a molecule's pharmacological activity. Using the design principle suggested by computational results, the team hit the motherlode in the lab, successfully developing a suite of 48 reactions that produce compounds potentially useful for novel drug development. However, researchers at ICReDD took things a big step further and used simulations to produce the general idea for an entirely unimagined reaction, effectively using computations to make the map itself. DOI: 10.1038/s44168-yĬomputer simulations are most often used as a guide so chemists can more efficiently work out the exact details of a general reaction idea they have in mind-much like a compass helps guide an explorer efficiently to a destination on their map. (Right) The successful reaction framework using pyridine and examples of the types of product compounds obtained. (Left) Reactions between difluorocarbene and numerous pairs of small molecules were simulated, predicting a N-heterocycle product fluorinated twice at the alpha carbon. Workflow of reaction discovery via in silico screening.

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